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Biomedical subjects

K Sjövall

Publications and source records attributed to K Sjövall.

At least 19 recordsLinked to original sources
PubMed2005

Graves' disease with moderate-severe endocrine ophthalmopathy-long term results of a prospective, randomized study of total or subtotal thyroid resection.

The optimal thyroid surgery to be performed in patients with Graves' disease and concomitant endocrine ophthalmopathy is a matter of debate. We randomly assigned 44 patients with moderate-severe eye signs in a trial of treatment with subtotal, leaving a small (approximately 2 g) thyroid remnant, or total thyroidectomy. At inclusion, the patients had been treated with antithyroid drugs, and corticosteroids been given to 12 (27%). All received postoperative thyroxine supplementation and were followed for 3 years at regular examinations. The eye disease improved in all cases, and throughout the study, the two groups did not differ with regard to subjective and objective eye symptoms and laboratory findings. At the study start, motility disturbances were present in 8 and 11 of the cases in the subtotal and total resection group and proptosis in 16 and 17, respectively. After 3 years, the corresponding data were 3 and 6 cases with motility defects and 16 and 15 cases with proptosis. Thyrotropin (TSH)-receptor antibody levels gradually fell and became nondetectable in 21 (49%). The surgical complication rate (permanent recurrent laryngeal nerve paresis and permanent hypoparathyroidism) was significantly higher in the total thyroidectomy group. The data indicate that in patients with Graves' disease and active endocrine ophthalmopathy, subtotal thyroidectomy, leaving a small thyroid remnant, will reduce the risk of surgical complications but not the beneficial effect of surgery.

Adult↗
PubMed2001

Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma.

BACKGROUND: Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables. METHODS: 1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables. FINDINGS: The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3.13 [95% CI 1.68-5.85], poorly vs well differentiated 8.89 [4.96-15.9]), followed by rupture before surgery (2.65 [1.53-4.56]), rupture during surgery (1.64 [1.07-2.51]), FIGO 1973 stage Ib vs Ia 1.70 [1.01-2.85]) and age (per year 1.02 [1.00-1.03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour. INTERPRETATION: Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries.

Cell Differentiation↗
PubMed2000

Long-term follow-up of the Stockholm screening study on ovarian cancer.

OBJECTIVES: Seventy percent of ovarian cancer is diagnosed at advanced stages. Having a method for early diagnosis is a very attractive concept. Several attempts have been made, using monoclonal antibody-based immunoassays, ultrasound, or combinations of both, to identify methods that might prove to be sufficiently sensitive and specific as a screening test. Despite promising results, a mortality study of a large population has yet to be completed due in part to the high cost involved. METHODS: One of the first studies aimed at devising a screening strategy for ovarian cancer used the CA 125 immunoassay followed by ultrasound. The study was performed in Stockholm from 1986 through 1988. Ten years now having passed, an analysis has been performed to further evaluate the results of that study. RESULTS: Screening led to the diagnosis of ovarian cancer in six patients, five of whom have since died of the disease. By searching the Cancer Registry, we were able to identify 20 ovarian cancer patients who developed the disease after the screening period. Of these, 12 died of the disease, 2 are alive with disease, and 6 have no evidence of disease following treatment. The median survival for patients diagnosed by screening was 100 months. Median survival for ovarian cancer patients identified subsequent to screening was 20 months. Although there was no difference in survival between these two groups, median survival was better for women diagnosed by screening (borderline significance, P = 0.059). CONCLUSION: These results indicate that a study of a large number of women with a sufficiently long observation time will be required to establish whether or not screening can reduce ovarian cancer mortality. Such a study may also provide insight into the natural history of ovarian cancer.

Adult↗
PubMed1999

Is there place for radiotherapy in the treatment of advanced ovarian cancer?

BACKGROUND AND PURPOSE: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. MATERIAL AND METHODS: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only. RESULTS: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. CONCLUSION: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

Aged↗
PubMed1997

Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro.

We tested 20 human carcinoma samples for the production of transforming growth factor beta (TGFbeta) in vitro. Tumour cell suspensions without obvious contamination with non-malignant cells were kept in culture conditions for 16 h and their supernatants were added to CCL-64 cells. The proliferation of these cells is inhibited by TGFbeta. According to this assay, the supernatants contained both active and latent TGFbeta. In addition, the supernatants were found to suppress the spontaneous cytotoxic function and activation of T-cell-enriched lymphocyte populations. A specific monoclonal antibody (mAb) counteracted these effects and therefore we concluded that they were mediated to a large extent by TGFbeta. In line with the results obtained with the supernatants, activation of lymphocytes could also be inhibited by tumour cells and their inhibitory effect was weaker in the presence of the TGFbeta-specific mAb. It is important to note that, when TGFbeta-specific mAb was added to autologous mixed lymphocyte/tumour cell cultures, lymphocyte activation occurred more often. These results thus substantiate the assumption that production of TGFbeta may help the survival of potentially immunogenic tumour cells in immunocompetent patients.

Carcinoma↗
PubMed1996

Biological malignancy grading in early-stage ovarian carcinoma.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Adult↗
PubMed1995

Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Aged↗
PubMed1992

Influences of diet and surgical trauma on serum alkaline DNase activity levels.

Changes in serum alkaline DNase activities might predict the therapeutic response in various malignant diseases. A decrease in serum alkaline DNase activity within days from the onset of therapy has been related to tumour necrosis and may be a possible sign of clinical response to effective treatment. To study if changes in serum alkaline DNase activity could be induced by non-tumour related tissue destruction, sera were collected on several occasions perioperatively in 18 patients undergoing surgery for benign gynaecological disease. Thirty apparently healthy women served as the control group. A significant decrease (P less than 0.001) in serum alkaline DNase activity was observed after an overnight fast in both groups of women. In contrast to the control women, the operated patients showed a significant decrease (P less than 0.001) in serum alkaline DNase activity throughout the operative period and 1 week postoperatively. We conclude that serum alkaline DNase activity is influenced by dietary factors as well as surgical trauma. These factors may limit the clinical usefulness of SADA in patients with cancer.

Adult↗
PubMed1992

Peri- and postoperative changes in serum levels of four tumor markers and three acute phase reactants in benign and malignant gynecological diseases.

Serum levels of squamous cell carcinoma antigen, carcinoembryonic antigen, CA 125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were determined peri- and postoperatively in patients undergoing surgery for benign gynecological disease (n = 18) and postoperatively in women operated for cervical carcinoma (n = 23). The only significant changes seen after premedication, during anesthesia and during surgery were a decrease in serum concentrations of alpha 1-antitrypsin and haptoglobin. We found no postoperative changes in the serum levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values. However, the latter analyte was influenced by smoking habits. Elevated levels of CA 125 and tissue polypeptide antigen were found in the cancer patients, predominantly within the first 1-3 weeks after surgery. These levels decreased to normal values within 4-6 weeks postoperatively. The median intraindividual coefficients of variation for the tumor markers ranged between 15% and 28% in 30 control women not having surgery. In general, it would seem advisable to wait 6 weeks after surgery before monitoring with CA 125 and TPA is started.

Acute-Phase Proteins↗
PubMed1992

Prognostic significance of pretreatment serum levels of squamous cell carcinoma antigen and CA 125 in cervical carcinoma.

Serum levels of squamous cell carcinoma antigen SCC, carcinoembryonic antigen CA 125, and tissue polypeptide antigen were determined in 142 patients with primary cervical carcinoma, 60 patients with precancerous lesions and in 129 healthy women. With regard to elevated tumour marker levels, specificity ranged from 94.6% to 97.7%. Sensitivity was highest (44.4%) for SCC. A stage relation was found for all tumour markers except for carcinoembryonic antigen. In stage Ib, SCC levels increased according to tumour volume. SCC, CA 125 or both markers were elevated in 7 of 8 patients with pelvic lymph node metastases compared with only 17 of 58 patients with negative nodes (P = 0.005). In a multivariate analysis, pretreatment serum levels of SCC and CA 125 were found to be significantly related to patient survival, in addition to stage. In cervical SCC, the risk of a fatal outcome increased 16 times with SCC levels > or = 4.5 ng/ml, compared with SCC levels < or = 1.3 ng/ml. We conclude that pretreatment serum levels of SCC may be of value as an adjunct to clinical staging. In addition, serum determinations of SCC and CA 125 seem to be useful in predicting the risk of pelvic lymph node metastases and as prognostic risk factors for disease outcome.

Adult↗
PubMed1992

Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer.

Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.

Adult↗
PubMed1991

Initial experiences with serum alkaline DNase activity in monitoring the effects of therapy for carcinoma of the uterine cervix.

The objective was to evaluate if variations in serum alkaline DNase activity (SADA) can predict the effects of therapy in women with early stages of primary cervical carcinoma. 29 out of 33 patients had no evidence of disease after therapy. Only 5 out of the 29 women showed increased SADA levels after therapy compared with the pretreatment SADA value. Of the 4 women with evidence of disease after therapy, 3 had unchanged or decreased SADA levels. We conclude that serum alkaline DNase activity seems to have little to offer in predicting the effects of treatment in stage I and stage II cervical carcinoma.

Deoxyribonucleases↗
PubMed1991

Pretreatment serum levels of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen in cervical carcinoma.

In order to evaluate the potentially additive information of some acute phase reactants to that provided by a general tumour marker, pretreatment concentrations of C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and tissue polypeptide antigen were determined in serum from healthy women, patients with dysplasia/or carcinoma in situ and patients with primary cervical carcinoma. Specificity varied from 95-100% and sensitivity from 16-29%. A correlation with clinical stage was found for all analytes except for alpha 1-antitrypsin. The latter was the most frequently elevated analyte in early Stages (11/43 in Stage Ib/IIa) and uniquely elevated in 7 cancer patients. Although tissue polypeptide antigen predominantly signaled in advanced stages, 3 women in early stages had elevated tissue polypeptide antigen levels. One of these women died and she was also the only woman with raised alpha 1-antitrypsin who died. It is discussed whether elevated tissue polypeptide levels might represent an unfavourable sign for the individual and if alpha 1-antitrypsin is a favourable sign in early stages of cervical carcinoma. C-reactive protein results were obscured in early stages of disease by the presence of intercurrent illness and the results were regarded as inconclusive. Haptoglobin and alpha 1-acid glycoprotein concentrations provided no additional information to serum alpha 1-antitrypsin levels. However, haptoglobin was elevated in 64% (36/56) of the women with dysplasia/carcinoma in situ of the cervix uteri.

Acute-Phase Proteins↗
PubMed1990

Stable isotope studies on steroid metabolism and kinetics: sulfates of 3 alpha-hydroxy-5 alpha-pregnane derivatives in human pregnancy.

The metabolism and production rates of 3 alpha-hydroxy-5 alpha-pregnan-20-one sulfate and the 3-sulfate and 3,20-disulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol in pregnant women were studied. The steroid sulfates were labeled with deuterium in the 3 beta,11,11- or 3 beta,11,11,20 beta-positions and were injected intravenously. The deuterium content of steroids in the monosulfate and disulfate fraction of plasma collected at different times after the injection was determined by capillary column gas chromatography/mass spectrometry. The injected steroid sulfates underwent oxidoreduction at C-20 and 16 alpha-hydroxylation. In addition, the 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol became hydroxylated at C-21. The pregnanediol and pregnanetriol monosulfates were also converted to disulfates. No evidence was obtained for a metabolic sequence involving hydrolysis, oxidoreduction, and resulfation at the C-3 position. Production rates and rates of metabolic transformations were determined using different one- and two-pool models. The production rate of the pregnanolone/pregnanediol monosulfate couple was 0.08 to 0.5 mmol/24 h, the variability probably depending both on individual factors and stage of pregnancy. The half-life time for oxidation and reduction at C-20 was 0.1 to 0.4 hours, reduction being the faster process. The half-life time for the turnover of the steroid skeleton was 1.3 to 3.3 hours. The injected steroid monosulfates were 16 alpha-hydroxylated at a rate of 1 to 8 mumol/24 h. A significant fraction of these 16 alpha-hydroxylated steroid sulfates, 0.5 to 25 mumol/24 h, was formed from other, probably unconjugated, precursors. The 16 alpha-hydroxylated steroid monosulfates underwent rapid oxidoreduction at C-20. The 3-sulfate of 5 alpha-pregnane-3 alpha,20 alpha-diol was hydroxylated at C-21. The production rate of 5 alpha-pregnane-3 alpha,20 alpha,21-triol 3-sulfate was 8 to 36 mumol/24 h in four women and 180 mumol/24 h in one woman, and this steroid was not formed from other precursors to a significant extent. 5 alpha-Pregnane-3 alpha,20 alpha-diol disulfate was a metabolic end product accounting for a major part of the elimination of the steroids injected. Its half-life time was 1.4 to 2.8 hours. The results show that the formation of sulfated steroids with a 3 alpha-hydroxy-5 alpha configuration may account for 50% of the metabolism of progesterone in late pregnancy.

Aryl Hydrocarbon Hydroxylases↗
PubMed1989

Serum alkaline DNase activity in normal or nonhospitalised individuals.

According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.

Adult↗
PubMed1989

Evaluation of seven different tumour markers for the establishment of tumour marker panels in gynecologic malignancies.

Seven tumour markers, i.e. squamous cell carcinoma antigen (SCC), cancer antigen 125 (CA 125), tissue polypeptide antigen (TPA), neopterin, C-reactive protein (CRP), carcinoembryonic antigen (CEA) and deoxythymidine kinase (TK) were analysed in sera from 104 women with benign and 61 women with malignant gynecologic diseases, in order to create tumour marker panels for various gynecologic malignancies, for monitoring and prediction of disease development. The incidence of elevated tumour marker levels, in cervical carcinoma was 78% when SCC, CA 125 and CEA were used. In ovarian carcinoma one of the markers CA 125, TPA and CEA was elevated in 91% and for endometrial carcinoma the best combination of markers was SCC, CA 125 and CEA (57%). No individual marker was superior to the above combinations. However, in patients with a fatal outcome of their malignant gynecologic disease (mean survival time from serum sampling was 16 months), the incidence of death was highest among those who had TPA elevated (91%) followed by neopterin (86%) and CRP (76%). Although intercurrent diseases affected tumour marker levels the markers picked up a majority of patients with a poor prognosis. This demonstrates the importance of interpreting tumour marker results against a background of detailed clinical information.

Adult↗
PubMed1988

Symptomatology of ovarian cancer.

The symptomatology of ovarian cancer was retrospectively reviewed in 362 patients. According to the stage at diagnosis, the disease was classified as early (stages IA-IIA) or advanced (stages IIB-IV). The most common initial symptoms were abdominal swelling and/or palpable tumour, pain and gastro-intestinal symptoms. The initial symptoms, however, were not necessarily those that prompted the patients to seek medical advice. Most were first seen by a gynecologist, which possibly explains the shortness of doctor's delay in the urbanized catchment region.

Female↗